Deep brain stimulation of the pedunculopontine nucleus modulates subthalamic pathological oscillations

Low frequency deep brain stimulation (DBS) of the pedunculopontine nucleus area (PPNa) has been proposed as a novel surgical target for gait dysfunction in the late stage of Parkinson's disease (PD). Since the mid-2000s, we have shown that intrasurgical delivery of stimulation in the pontine tegmentum affects the firing activity in the subthalamic nucleus (STN), but its effect on STN oscillatory rhythms has not been studied. Neuronal oscillations detected by local field potential (LFPs) have great importance, since they express complex movement-related behavior such as locomotion. Therefore, we examined the effect of three PPNa-DBS stimulation protocols (at 10, 25 and 80 Hz) on the STN oscillatory activity of PD patients. We focused on the anti-kinetic beta (β, 15-30 Hz), the pro-kinetic gamma (γ, 60-90 Hz) and "gait-related" alpha (α, 7-12 Hz) bands. We hypothesized that modulation of STN oscillations might have clinical relevance in the PPNa-mediated effects. PPNa stimulation at 25 and 80 Hz decreased the power of the STN β band by 33.94 and 40.22%, respectively. PPNa-DBS did not affect the other two bands with a tendency to suppress α power, while γ oscillation increased. Our results suggest that the anti-kinetic β band is the oscillation most sensitive to PPNa-DBS despite the negligible clinical efficacy on bradykinesia. However, how these changes interact reciprocally with the cortex or are counterbalanced by lower brainstem/spinal pathways remain to be elucidated. Our observation might turn out to be helpful in new protocols designed with adaptive DBS supporting the addition of PPN implantation in PD patients experiencing declining efficacy of STN-DBS.